L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells
L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells
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DOI：
10.1016/j.ygyno.2006.08.038
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Altevogt, Peter
中科院分区：
文献类型：
--
作者：
Stoeck, Alexander;Gast, Daniela;Altevogt, Peter
目的。抗凋亡是癌症进展的一个标志，这是在卵巢癌中经常观察到的现象。我们之前报道过，L1黏附分子（CD171）在卵巢癌和子宫内膜癌中过度表达，并且L1的表达是不良预后的一个预测指标。我们研究了L1在抗凋亡中的可能作用。
方法。我们使用L1转染细胞和卵巢癌细胞系，并通过不同的刺激物如C2 - 神经酰胺、星形孢菌素、顺铂或缺氧来诱导凋亡。
结果。我们发现表达L1的细胞对凋亡更具抗性。在HEK293细胞中，L1的表达导致细胞外调节蛋白激酶（ERK）、黏着斑激酶（FAK）和p21激活激酶（PAK）持续磷酸化。可溶性L1仅部分挽救HEK - 293细胞免于凋亡。在表达L1的HEK293细胞中，凋亡刺激处理使抗凋亡分子Bcl - 2更大程度地上调。在卵巢癌细胞系OVMz中，通过RNA干扰使L1缺失使细胞对凋亡诱导敏感。在L1敲低后，未观察到ERK或FAK激活的变化。用顺铂筛选m130卵巢癌细胞或SW707结肠癌细胞导致L1表达上调。
结论。我们的结果表明L1的表达与卵巢癌的化疗耐药性之间存在联系。鉴于L1在细胞运动和侵袭中的既定作用，顺铂治疗后L1的上调可能表明肿瘤具有更恶性的表型。（c）2006爱思唯尔公司。保留所有权利。
Objective. Apoptosis resistance is a hallmark of cancer progression, a phenomenon frequently observed in ovarian carcinoma. We reported previously, that L1 adhesion molecule (CD171) is overexpressed in ovarian and endometrial carcinomas and that L1 expression is a predictor of poor outcome. We investigated a possible role of L1 in apoptosis resistance.Methods. We used L1 transfectants and ovarian carcinoma cell lines and induced apoptosis by different stimuli such as C2-ceramide, staurosporine, cisplatin or hypoxia.Results. We found that cells expressing L1 are more resistant against apoptosis. In HEK293 cells, L1-expresssion leads to a sustained ERK, FAK and PAK phosphorylation. Soluble L1 only partially rescued HEK-293 cells from apoptosis. Treatment with apoptotic stimuli upregulated the anti-apoptotic molecule Bcl-2 to a greater extend in HEK293 cells expressing L1. In the ovarian carcinoma cell line OVMz, the depletion of L1 by RNA interference sensitized cells for apoptosis induction. No changes in activation of ERK or FAK were observed after L1 knockdown. The selection of m130 ovarian carcinoma or SW707 colon carcinoma cells with cisplatin leads to upregulated expression of L1.Conclusions. Our results suggest a link between L1 expression and chemoresistance of ovarian carcinomas. Upregulation of L1 after cisplatin treatment might indicate a more malignant tumor phenotype given the established role of L1 in cell motility and invasion. (c) 2006 Elsevier Inc. All rights reserved.